title: Licorice-derived dehydroglyasperin C increases MKP-1 expression and suppresses inflammation-mediated neurodegeneration.
abstract: Recent studies have demonstrated that microglial hyperactivation-mediated neuroinflammation is involved in the pathogenesis of several neurodegenerative diseases. Thus, inhibiting microglial production of the neurotoxic mediator tumor necrosis factor-α (TNF-α) is considered a promising strategy to protect against neurodegeneration. Here, we investigated the inhibitory effect of licorice-derived dehydroglyasperin C (DGC) on lipopolysaccharide (LPS)-induced TNF-α production and inflammation-mediated neurodegeneration. We found that DGC pre-treatment attenuated TNF-α production in response to LPS stimulation of BV-2 microglia. DGC pre-treatment attenuated LPS-induced inhibitor of κB-α (IκB-α) and p65 phosphorylation and decreased the DNA binding activity of nuclear factor-κB (NF-κB). DGC pre-treatment also inhibited LPS-mediated phosphorylation of p38 mitogen-activated protein kinases (MAPKs) and extracellular signal-regulated kinase (ERK). Interestingly, DGC treatment of BV-2 microglia significantly increased MAPK phosphatase 1 (MKP-1) mRNA and protein expression, which is a phosphatase of p38 MAPK and ERK, suggesting that the DGC-mediated increase in MKP-1 expression might inhibit LPS-induced MAPKs and NF-κB activation and further TNF-α production. We also found that LPS-mediated microglial neurotoxicity can be attenuated by DGC. The addition of conditioned media (CM) from DGC- and LPS-treated microglia to neurons helped maintain healthy cell body and neurite morphology and increased the number of microtubule-associated protein 2-positive cells and the level of synaptophysin compared to treatment with CM from LPS-treated microglia. Taken together, these data suggest that DGC isolated from licorice may inhibit microglia hyperactivation by increasing MKP-1 expression and acting as a potent anti-neurodegenerative agent.
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Jaekyoon
authors.initials: J
authors.lastname: Kim
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Jaesung
authors.initials: J
authors.lastname: Shim
authors.forename: Siyoung
authors.initials: S
authors.lastname: Lee
authors.forename: Jisung
authors.initials: J
authors.lastname: Kim
authors.forename: Soon Sung
authors.initials: SS
authors.lastname: Lim
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Hyong Joo
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D001483:Base Sequence; D001578:Benzopyrans / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D017931:DNA Primers; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D006035:Glycyrrhiza / Q000737:chemistry*; D007249:Inflammation / Q000150:complications / Q000517:prevention & control*; D051379:Mice; D017628:Microglia / Q000502:physiology; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001578:Benzopyrans; D017931:DNA Primers; C548688:dehydroglyasperin C; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1
keywords: CM; DGC; Dehydroglyasperin C; ERK; IκB-α; LPS; MAP2; MAPK; MKP; Microglia; Mitogen-activated protein kinase phosphatase-1 (MKP-1); NF-κB; Neurodegeneration; Neuron; SFN; TNF-α; Tumor necrosis factor-α (TNF-α); conditioned media; dehydroglyasperin C; extracellular signal-regulated kinase; inhibitor of kappa B-α; lipopolysaccharide; microtubule-associated protein 2; mitogen-activated protein kinase; mitogen-activated protein kinase phosphatase; nuclear factor-kappa B; sulforaphane; tumor necrosis factor-α